PT - JOURNAL ARTICLE
AU - Rathore, Khizr I.
AU - Berard, Jennifer L.
AU - Redensek, Adriana
AU - Chierzi, Sabrina
AU - Lopez-Vales, Ruben
AU - Santos, Manuela
AU - Akira, Shizuo
AU - David, Samuel
TI - Lipocalin 2 Plays an Immunomodulatory Role and Has Detrimental Effects after Spinal Cord Injury
DP - 2011 Sep 21
TA - The Journal of Neuroscience
PG - 13412--13419
VI - 31
IP - 38
4099 - http://www.jneurosci.org/content/31/38/13412.short
4100 - http://www.jneurosci.org/content/31/38/13412.full
SO - J. Neurosci.2011 Sep 21; 31
AB - Lipocalin 2 (Lcn2) plays an important role in defense against bacterial infection by interfering with bacterial iron acquisition. Although Lcn2 is expressed in a number of aseptic inflammatory conditions, its role in these conditions remains unclear. We examined the expression and role of Lcn2 after spinal cord injury (SCI) in adult mice by using a contusion injury model. Lcn2 expression at the protein level is rapidly increased 12-fold at 1 d after SCI and decreases gradually thereafter, being three times as high as control levels at 21 d after injury. Lcn2 expression is strongly induced after contusion injury in astrocytes, neurons, and neutrophils. The Lcn2 receptor (Lcn2R), which has been shown to influence cell survival, is also expressed after SCI in the same cell types. Lcn2-deficient (Lcn2−/−) mice showed significantly better locomotor recovery after spinal cord contusion injury than wild-type (Lcn2+/+) mice. Histological assessments indicate improved neuronal and tissue survival and greater sparing of myelin in Lcn2−/− mice after contusion injury. Flow cytometry showed a decrease in neutrophil influx and a small increase in the monocyte population in Lcn2−/− injured spinal cords. This change was accompanied by a reduction in the expression of several pro-inflammatory chemokines and cytokines as well as inducible nitric oxide synthase early after SCI in Lcn2−/− mice compared with wild-type animals. Our results, therefore, suggest a role for Lcn2 in regulating inflammation in the injured spinal cord and that lack of Lcn2 reduces secondary damage and improves locomotor recovery after spinal cord contusion injury.